Methoxychlor mimics the action of 17β-estradiol on induction of uterine epidermal growth factor receptors in immature female rats

Epidermal growth factor (EGF) and its receptor (EGF-R) have been implicated as mediators for estrogen induced cellular growth. This study examines whether the action of the estrogenic pesticide methoxychlor (MXC) parallels the action of 17β-estradiol (E 2) on uterine EGF-R. Administration of 20 μg E 2/sexually immature female rat increased 125I-EGF binding to membranes extracted from whole uteri 175% over endogenous levels, while 500 mg MXC/kg led to a 156% increase. E 2 in both 20 and 40 μg/rat doses and 500 mg MXC/kg led to maximal stimulation over endogenous levels, 12-h posttreatment. Rats were treated with E 2, MXC, or vehicle plus 100 μg actinomycin-D (ACT-D) or 100 μg cycloheximide (CYCLO) per rat to determine if mRNA transcription and translation are involved in the increased EGF-R binding following estrogenic treatment. Only ACT-D inhibited the estrogenic stimulation of EGF-R binding, resulting in a 44% decrease when given concurrently with E 2 or MXC, suggesting transcription is required. Additionally, ACT-D decreased endogenous receptor levels by 55%. No other differences were detected. When EGF-R binding data were analyzed by the method of Scatchard, both E 2 and MXC, at maximal dosages, elevated uterine EGF-R binding sites by over 200% after 12 h as measured by maximal binding ( B max) with no significant difference in dissociation constant ( K d) values. These results demonstrate that both E 2 and MXC can stimulate the number of EGF-R binding sites without significantly altering the receptor binding affinity ( K d). Further, this stimulation is time dependent and is affected by dose.